19-38883729-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_012237.4(SIRT2):c.529G>A(p.Gly177Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000052 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
SIRT2
NM_012237.4 missense
NM_012237.4 missense
Scores
5
7
1
Clinical Significance
Conservation
PhyloP100: 6.95
Genes affected
SIRT2 (HGNC:10886): (sirtuin 2) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.922
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIRT2 | NM_012237.4 | c.529G>A | p.Gly177Arg | missense_variant | 9/16 | ENST00000249396.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIRT2 | ENST00000249396.12 | c.529G>A | p.Gly177Arg | missense_variant | 9/16 | 1 | NM_012237.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251380Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135870
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GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727186
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152252Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74438
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2022 | The c.529G>A (p.G177R) alteration is located in exon 9 (coding exon 9) of the SIRT2 gene. This alteration results from a G to A substitution at nucleotide position 529, causing the glycine (G) at amino acid position 177 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Pathogenic
Polyphen
1.0
.;D;D;.;.;.
Vest4
MutPred
0.78
.;Gain of solvent accessibility (P = 0.019);.;.;.;.;
MVP
MPC
0.89
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at